The present invention is related to methods for treating patients suffering from physiological, psychosomatic, neurological or psychiatric disorders. The methods include the administration of certain peptides.
Endogenous depression is thought to be a genetically determined biochemical disorder which can result in an inability to deal with stress. Treatment for endogenous depression includes electroconvulsive therapy and/or drug therapy. Drugs administered for therapeutic treatment of depression include tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, xe2x80x9csecond-generationxe2x80x9d antidepressants, and selective serotonin reuptake inhibitors (SSRIs).
Tricyclic antidepressants (TPAs) have been the drug of first choice in treating endogenous depression for over three decades. However, these drugs have limited efficacy in that 40 to 60% of patients receiving tricyclic drugs do not respond favorably. The side effects of the tricyclics are numerous, including cholinergic blockage, cardiac complications, allergic reactions, dry mouth, constipation, blurred vision and tachycardia. Tricyclic antidepressants are characterized by a three-ringed structure, and include imipramine, desipramine, amitriptyline, nortriptyline, protriptyline, doxepin and trimipramine. The tricyclic antidepressants are metabolized through the mixed-function oxidase system, and the metabolites of the tricyclic antidepressants are also pharmacologically active compounds.
The MAO inhibitors have been available for treatment of depression since the 1950""s. MAO inhibitors are classified either as hydrazides, which contain by a Cxe2x80x94Nxe2x80x94N moiety (e.g., phenelzine and isocarboxazide) or nonhydrazides (e.g., tranylcypromine). MAO inhibitors have not gained wide acceptance due to serious side effects.
The second-generation antidepressants include amoxapine, maprotiline, nefasodone, trazodone and bupropion. The second-generation antidepressants a produce a variety of effects on serotonergic and dopaminergic activity.
The selective serotonin reuptake inhibitors, including fluoxetine, sertraline, paroxetine, fluoroxamine, and citalopram, are believed to work primarily by a serotonergic mechanism. They are safer and better tolerated than the TCAs and MAOIs, but are probably not as effective in more serious depression and have troublesome side effects such as sexual dysfunction in about 40% of patients. In addition, about thirty percent of patients do not have a favorable response with the SSRIs.
The tripeptide MIF, otherwise known as melanocyte stimulating inhibitory factor, which is represented by the chemical formula of prolyl-leucyl-glycinamide or Pro-Leu-Gly-NH2, has been shown to produce numerous non-endocrine effects on the brain. The MIF tripeptide has also been shown to be active in a number of animal models for depression.
A need remains for new and/or improved methods and compositions for treating psychiatric and neurological disorders. In particular, it is desired to provide such new methods and compositions while reducing and preferably minimizing undesired side effects.
The present invention provides compositions and methods for treating physiological, psychosomatic, neurological or psychiatric disorders. The compositions are peptides. The compositions and methods are useful in treating patients suffering from neurological or psychiatric disorders.
It has been found that peptides described herein are potentially useful in treating a variety of physiological, psychosomatic, neurological and psychological disorders, including bipolar disorder, seasonal affective disorder, eating disorders such as bulimia, anorexia nervosa and exogenous obesity, chronic fatigue syndrome, fibromyalgia, sexual dysfunction, anxiety disorders, attention deficit disorder, Parkinson""s disease, depression accompanying schizophrenia, jet lag syndrome and addiction disorders including alcohol dependence. It has further been found that the methods and compositions disclosed herein are effective in treating depression in patients that are deemed unresponsive to conventional anti-depressant medications. Such patients may be referred to as xe2x80x9crefractoryxe2x80x9d patients.
It has further been found that the methods and compositions disclosed herein are useful in treating patients suffering from anxiety. In treating patients suffering from anxiety, the compositions disclosed herein may be administered alone or in combination with other pharmaceutical compounds.
According to one aspect of the invention, there is provided a method for treating a patient suffering from bipolar disorder. The method comprises administering to the patient a pharmaceutically effective amount of one or more of the peptides disclosed herein.
According to another aspect of the invention, there is provided a method for treating a patient suffering from seasonal affective disorder. The method comprises administering to the patient a pharmaceutically effective amount of one or more of the peptides disclosed herein.
According to another aspect of the invention, there is provided a method for treating a patient suffering from an eating disorder. The method comprises administering to the patient a pharmaceutically effective amount of one or more of the peptides disclosed herein.
According to another aspect of the invention, there is provided a method for treating a patient suffering from fibromyalgia or chronic fatigue syndrome. The method comprises administering to the patient a pharmaceutically effective amount of one or more of the peptides disclosed herein.
According to another aspect of the invention, there is provided a method for treating a patient suffering from sexual dysfunction. The method comprises administering to the patient a pharmaceutically effective amount of one or more of the peptides disclosed herein.
According to one another aspect of the invention, there is provided a method for treating a patient suffering from anxiety disorder. The method comprises administering to the patient a pharmaceutically effective amount of one or more of the peptides disclosed herein.
According to another aspect of the invention, there is provided a method for treating a patient suffering from attention deficit disorder. The method comprises administering to the patient a pharmaceutically effective amount of one or more of the peptides disclosed herein.
According to another aspect of the invention, there is provided a method for treating a patient suffering from Parkinson""s disease. The method comprises administering to the patient a pharmaceutically effective amount of one or more of the peptides disclosed herein.
According to another aspect of the invention, there is provided a method for treating a patient suffering from depression accompanying schizophrenia. The method comprises administering to the patient a pharmaceutically effective amount of one or more of the peptides disclosed herein.
Peptides for use in the methods described herein include compounds made by modifications, substitutions, additions and/or deletions to a MIF core structure, Pro-Leu-Gly-NH2, also referred to herein as xe2x80x9cmodified MIF compoundsxe2x80x9d. The modified MIF compounds have been found to have pharmacological activity and to be useful in treating a variety of neurological or psychiatric disorders.
The compounds disclosed herein may be administered by a variety of routes, including subcutaneously, intramuscularly, orally, sublingually, and transdermally.